Association of a pH-sensitive peptide with membrane vesicles: role of amino acid sequence

Parente, Roberta A.; Nádasdi, László; Subbarao, Nanda K.; Szoka, Francis C.

doi:10.1021/bi00489a030

Cited by 121 publications

(86 citation statements)

References 32 publications

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“…Parente et al examined the membrane-destabilizing effect of GALA peptide, on the experimental model of lipid biolayer vesicles of egg phosphatidylcholine in a lipid/peptide molar ratio of 500/1. 84 At pH 5.0, leakage of contents was detected from 100% of the vesicles, but was abrogated at pH 7.5. This is thought to result from pH-dependent conformational changes of the peptide, which binds to the bilayer at pH 5.0, but not at neutral pH.…”

Section: Proteins and Polypeptidesmentioning

confidence: 95%

Non-viral gene delivery in skeletal muscle: a protein factory

Lu¹,

Bou‐Gharios²,

Partridge³

2003

Gene Ther

168

109

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Ever since the publication of the first reports in 1990 using skeletal muscle as a direct target for expressing foreign transgenes, an avalanche of papers has identified a variety of proteins that can be synthesized and correctly processed by skeletal muscle. The impetus to the development of such applications is not only amelioration of muscle diseases, but also a range of therapeutic applications, from immunization to delivery of therapeutic proteins, such as clotting factors and hormones. Although the most efficient way of introducing transgenes into muscle fibres has been by a variety of recombinant viral vectors, there are potential benefits in the use of non-viral vectors. In this review we assess the recent advances in construction and delivery of naked plasmid DNA to skeletal muscle and highlight the options available for further improvements to raise efficiency to therapeutic levels.

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Section: Proteins and Polypeptidesmentioning

confidence: 95%

Non-viral gene delivery in skeletal muscle: a protein factory

Lu¹,

Bou‐Gharios²,

Partridge³

2003

Gene Ther

168

109

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“…Leakage from lipid vesicles is initiated within 2 s after pH is lowered below 6, and is rapidly terminated when pH is raised to 7.5 (Parente et al 1990a). The pH-dependent leakage activity was greatly influenced by the positioning of the amino acids (Parente et al 1990b). Figure 2 compares the helical grids of GALA and LAGA.…”

Section: Synthetic Amphipathic Peptides Ph-dependent Membrane Destabimentioning

confidence: 99%

Polycation gene delivery systems: escape from endosomes to cytosol

Cho

Kim

Park

2003

Journal of Pharmacy and Pharmacology

336

169

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Clinical success of gene therapy based on oligonucleotides (ODNs), ribozymes, RNA and DNA will be greatly dependent on the availability of effective delivery systems. Polycations have gained increasing attention as a non-viral gene delivery vector in the past decades. Significant progress has been made in understanding complex formation between polycations and nucleic acids, entry of the complex into the cells and subsequent entry into the nucleus. Sophisticated molecular architectures of cationic polymers have made the vectors more stable and less susceptible to binding by enzymes or proteins. Incorporation of specific ligands to polycations has resulted in more cell-specific uptake by receptor-mediated mechanisms. However, there are still other barriers limiting the transfection efficiency of polycation gene delivery systems. There is a consensus that polycation-DNA complexes (polyplexes) enter cells via the endocytotic pathway. It is not clearly understood, however, how the polyplexes escape (if they do) from endosomes, how DNA is released from the polyplexes or how the released DNA is expressed. The primary focus of this article is to review various polycation gene delivery systems, which are designed to translocate DNA from endosomes into cytosol. Many polycation gene delivery systems have tried to mimic the mechanisms that viruses use for the endosomal escape. Polycation gene delivery systems are usually coupled with synthetic amphipathic peptides mimicking viral fusogenic peptides, histidine-based gene delivery systems for pH-responsive endosomal escape, polycations with intrinsic endosomolytic activity by the proton sponge mechanism and polyanions to mimic the anionic amphiphilic peptides.

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“…carboxylic group) that act as a stabilizer at neutral pH [4][5][6]. More recently, the use of novel pH-sensitive lipids, synthetic fusogenic peptides/proteins either encapsulated [7,8] or incorporated in the lipid bilayer [9][10][11][12][13], and association of pH-sensitive polymers with liposomes [14 -16] have been reported.…”

Section: Introductionmentioning

confidence: 99%

On the formulation of pH-sensitive liposomes with long circulation times

Simões

Moreira

Fonseca

et al. 2004

Advanced Drug Delivery Reviews

434

244

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Strategies used to enhance liposome-mediated drug delivery in vivo include the enhancement of stability and circulation time in the bloodstream, targeting to specific tissues or cells, and facilitation of intracytoplasmic delivery. pH-sensitive liposomes have been developed to mediate the introduction of highly hydrophilic molecules or macromolecules into the cytoplasm. These liposomes destabilize under acidic conditions found in the endocytotic pathway, and usually contain phosphatidylethanolamine (PE) and titratable stabilizing amphiphiles. Formulations without PE have also been developed. Encapsulated compounds are thought to be transported into the cytoplasm through destabilization of or fusion with the endosome membrane. Incorporation of a low mole percentage of poly(ethylene glycol) (PEG)-conjugated lipids into pHsensitive liposomes confers prolonged circulation times to these liposomes, which are otherwise cleared rapidly. While the incorporation of PEG -lipids reduces the pH-dependent release of encapsulated fluorescent markers in vitro, it does not hinder the cytoplasmic delivery of the markers per cell-associated liposome. This suggests that intracellular delivery is not dictated simply by the destabilization of the liposomes. Antibodies or ligands to cell surface receptors can be coupled to pH-sensitive or sterically stabilized pH-sensitive liposomes for targeting. pH-sensitive liposomes have been used to deliver anticancer drugs, antibiotics, antisense oligonucleotides, ribozymes, plasmids, proteins and peptides to cells in culture or in vivo. D

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Association of a pH-sensitive peptide with membrane vesicles: role of amino acid sequence

Cited by 121 publications

References 32 publications

Non-viral gene delivery in skeletal muscle: a protein factory

Non-viral gene delivery in skeletal muscle: a protein factory

Polycation gene delivery systems: escape from endosomes to cytosol

On the formulation of pH-sensitive liposomes with long circulation times

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